chr5-129905295-G-A

Variant names:

• chr5-129905295-G-A
• rs775342100
• NM_175856.5:c.466G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_175856.5(CHSY3):​c.466G>A​(p.Gly156Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 1,331,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G156R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: CHSY3 NM_175856.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98
• Publications: 0 publications found

Genes affected

CHSY3 (HGNC:24293): (chondroitin sulfate synthase 3) CSS3 is a glycosyltransferase that has both glucuronyltransferase and N-acetylgalactosaminyltransferase activities (Yada et al., 2003 [PubMed 12907687]).[supplied by OMIM, Mar 2008]

ENSG00000251680 (HGNC:58253):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26651108).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY3	NM_175856.5	c.466G>A	p.Gly156Ser	missense_variant	Exon 1 of 3	ENST00000305031.5	NP_787052.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHSY3	ENST00000305031.5	c.466G>A	p.Gly156Ser	missense_variant	Exon 1 of 3	1	NM_175856.5	ENSP00000302629.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000150 AC: 2 AN: 1331148 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 652764

African (AFR) AF: 0.00 AC: 0 AN: 30048

American (AMR) AF: 0.00 AC: 0 AN: 29636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21376

East Asian (EAS) AF: 0.00 AC: 0 AN: 35262

South Asian (SAS) AF: 0.00 AC: 0 AN: 71260

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4798

European-Non Finnish (NFE) AF: 0.00000190 AC: 2 AN: 1051176

Other (OTH) AF: 0.00 AC: 0 AN: 55434

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.0
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.46	N
REVEL	Benign	0.082
Sift	Benign	0.25	T
Sift4G	Benign	0.18	T
Polyphen		0.69	P
Vest4		0.30
MutPred		0.23		Gain of phosphorylation at G156 (P = 0.0092);
MVP		0.78
MPC		2.2
ClinPred		0.87	D
GERP RS		4.2
Varity_R		0.16
gMVP		0.37
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs775342100; hg19: chr5-129240988;